Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression.

BACKGROUND: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied. METHODS: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression. RESULTS: Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups. CONCLUSIONS: In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.).

Remission and recurrence in bipolar disorder: The data from health outcomes and patient evaluations in bipolar disorder (HOPE-BD) study.

BACKGROUND: The HOPE-BD was a naturalistic study established to follow individuals in Canada seeking treatment for bipolar disorder (BD). The study aimed to examine the course of BD and describe how clinical and sociodemographic factors are associated with outcomes. METHODS: Individuals with BD had their clinical data recorded at enrolment and were naturalistically treated. Participant were followed for up to four years, and visits occurred at least once every three months. We investigated the longitudinal outcomes with logistic, Cox, and quantile regressions. RESULTS: Among the 354 participants, 57.3% had BD type I. Depression as first episode, younger ages at onset and older ages of the first professional help predicted longer delays in correct diagnosis. Among the symptomatic patients at baseline, the median time to remission was 10.9 months. Comorbid alcohol use disorder and the severity of baseline depressive symptoms predicted longer times to remission. Among the euthymic participants, the median time to recurrence was 14.5 months. History of anxiety disorder and younger ages at onset predicted shorter times to recurrence. Baseline depression scores predicted recurrence in euthymic patients. LIMITATIONS: We did not investigate the predictors of each polarity. Our findings may not apply to individuals followed in non-specialised outpatient services. CONCLUSION: Our study reinforces the necessity of early diagnosis and interventions, as well as the importance of treating depressive symptoms and comorbidities.

Diagnosis of bipolar disorder in primary and secondary care: what have we learned over a 10-year period?

BACKGROUND: Studies suggest that misdiagnosis of bipolar disorders (BD) is frequent in primary care. This study aimed to evaluate agreement between referral for BD by general practitioners (GP) and BD diagnosis by secondary care psychiatrists, and to evaluate the impact of age, gender, and BD type on agreement. METHODS: The study was conducted at Hôpital du Sacré-Coeur de Montréal׳s "Module Evaluation/Liaison" (MEL), which establishes/clarifies psychiatric diagnoses requested mainly from GPs and directs patients to appropriate treatment and care. Socio-demographic variables, reason for referral, and psychiatric diagnosis were compiled for patients assessed from 1998 to 2010. GP-psychiatrist agreement was established for BD type, gender, and age group (18-25, 26-35, 36-45, >45) using Cohen׳s Kappa coefficient (Κ). RESULTS: From 1998 to 2010, MEL psychiatrists received 18,111 requests and carried out 10,492 (58%) assessments. There were 583 referrals for BD suspicion, while 640 assessments (6.1%) received a BD diagnosis (40.3% type I, 40.5% type II). The overall K was 0.35 (95% CI [0.31, 0.38]), and was significantly higher for type I than type II (I=0.35, 95% CI [0.30, 0.39]; II=0.25, 95% CI [0.21, 0.30]), though age group and gender had no impact. LIMITATIONS: Reasons for referral were converted into keywords and categories to facilitate agreement analyses. Only the main psychiatric diagnosis was available. CONCLUSIONS: Our study suggests diagnosing BD remains strenuous, regardless of age and gender, though BD type I seems better understood by primary care GPs. The true measure of BD diagnosis remains a critical issue in clinical practice.

Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies.

Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.